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Maternal Low-protein Diet Alters Ovarian Expression of Folliculogenic and Steroidogenic Genes and Their Regulatory MicroRNAs in Neonatal Piglets

  • Sui, Shiyan (Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University) ;
  • Jia, Yimin (Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University) ;
  • He, Bin (Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University) ;
  • Li, Runsheng (Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University) ;
  • Li, Xian (Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University) ;
  • Cai, Demin (Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University) ;
  • Song, Haogang (Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University) ;
  • Zhang, Rongkui (Shanghai Farm of Bright Food (Group) Co., Ltd.) ;
  • Zhao, Ruqian (Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University)
  • Received : 2014.05.08
  • Accepted : 2014.08.23
  • Published : 2014.12.01

Abstract

Maternal malnutrition during pregnancy may give rise to female offspring with disrupted ovary functions in adult age. Neonatal ovary development predisposes adult ovary function, yet the effect of maternal nutrition on the neonatal ovary has not been described. Therefore, here we show the impact of maternal protein restriction on the expression of folliculogenic and steroidogenic genes, their regulatory microRNAs and promoter DNA methylation in the ovary of neonatal piglets. Sows were fed either standard-protein (SP, 15% crude protein) or low-protein (LP, 7.5% crude protein) diets throughout gestation. Female piglets born to LP sows showed significantly decreased ovary weight relative to body weight (p<0.05) at birth, which was accompanied with an increased serum estradiol level (p<0.05). The LP piglets demonstrated higher ratio of bcl-2 associated X protein/B cell lymphoma/leukemia-2 mRNA (p<0.01), which was associated with up-regulated mRNA expression of bone morphogenic protein 4 (BMP4) (p<0.05) and proliferating cell nuclear antigen (PCNA) (p<0.05). The steroidogenic gene, cytochrome P450 aromatase (CYP19A1) was significantly down-regulated (p<0.05) in LP piglets. The alterations in ovarian gene expression were associated with a significant down-regulation of follicle-stimulating hormone receptor mRNA expression (p<0.05) in LP piglets. Moreover, three microRNAs, including miR-423-5p targeting both CYP19A1 and PCNA, miR-378 targeting CYP19A1 and miR-210 targeting BMP4, were significantly down-regulated (p<0.05) in the ovary of LP piglets. These results suggest that microRNAs are involved in mediating the effect of maternal protein restriction on ovarian function through regulating the expression of folliculogenic and steroidogenic genes in newborn piglets.

Keywords

Folliculogenesis;Steroidogenesis;Maternal Dietary Protein;MicroRNA;Ovary;Neonatal Piglet

References

  1. Chen, Y., W. N. Jefferson, R. R. Newbold, E. Padilla-Banks, and M. E. Pepling. 2007. Estradiol, progesterone, and genistein inhibit oocyte nest breakdown and primordial follicle assembly in the neonatal mouse ovary in vitro and in vivo. Endocrinology 148:3580-3590. https://doi.org/10.1210/en.2007-0088
  2. Baley, J. and J. Li. 2012. Micrornas and ovarian function. J. Ovarian Res. 5:8. https://doi.org/10.1186/1757-2215-5-8
  3. Bernal, A. B., M. H. Vickers, M. B. Hampton, R. A. Poynton, and D. M. Sloboda. 2010. Maternal undernutrition significantly impacts ovarian follicle number and increases ovarian oxidative stress in adult rat offspring. Plos One. 5(12):e15558. https://doi.org/10.1371/journal.pone.0015558
  4. Camp, T. A., J. O. Rahal, and K. E. Mayo. 1991. Cellular localization and hormonal regulation of follicle-stimulating hormone and luteinizing hormone receptor messenger rnas in the rat ovary. Mol. Endocrinol. 5:1405-1417. https://doi.org/10.1210/mend-5-10-1405
  5. da Silva Faria, T., C. da Fonte Ramos, and F. J. B. Sampaio. 2004. Puberty onset in the female offspring of rats submitted to protein or energy restricted diet during lactation. J. Nutr. Biochem. 15:123-127. https://doi.org/10.1016/j.jnutbio.2003.08.011
  6. Faria, T. S., F. B. Brasil, F. J. B. Sampaio, and C. F. Ramos. 2010. Effects of maternal undernutrition during lactation on estrogen and androgen receptor expressions in rat ovary at puberty. Nutrition 26:993-999. https://doi.org/10.1016/j.nut.2009.09.027
  7. da Silva Faria, T., F. de Bittencourt Brasil, F. J. Sampaio, and C. da Fonte Ramos. 2008. Maternal malnutrition during lactation alters the folliculogenesis and gonadotropins and estrogen isoforms ovarian receptors in the offspring at puberty. J. Endocrinol. 198:625-634. https://doi.org/10.1677/JOE-08-0121
  8. Ding W., W. Wang, B. Zhou, W. Zhang, P. Huang, F. Shi, and K. Taya. 2010. Formation of primordial follicles and immunolocalization of PTEN, PKB and FOXO3a proteins in the ovaries of fetal and neonatal pigs. J. Reprod. Dev. 56:162-168. https://doi.org/10.1262/jrd.09-094H
  9. Durlej, M., K. Knapczyk-Stwora, M. Duda, J. Galas, and M. Slomczynska. 2011. The expression of FSH receptor (FSHR) in the neonatal porcine ovary and its regulation by flutamide. Reprod. Domest. Anim. 46:377-384. https://doi.org/10.1111/j.1439-0531.2010.01673.x
  10. Fiedler, S. D., M. Z. Carletti, X. Hong, and L. K. Christenson. 2008. Hormonal regulation of microrna expression in periovulatory mouse mural granulosa cells. Biol. Reprod. 79:1030-1037. https://doi.org/10.1095/biolreprod.108.069690
  11. Fire, A., S. Xu, M. K. Montgomery, S. A. Kostas, S. E. Driver, and C. C. Mello. 1998. Potent and specific genetic interference by double-stranded rna in caenorhabditis elegans. Nature 391(6669):806-811. https://doi.org/10.1038/35888
  12. Fortune, J., R. Cushman, C. Wahl, and S. Kito. 2000. The primordial to primary follicle transition. Mol. Cell. Endocrinol. 163:53-60. https://doi.org/10.1016/S0303-7207(99)00240-3
  13. Godfrey, K. M., P. D. Gluckman, and M. A. Hanson. 2010. Developmental origins of metabolic disease: Life course and intergenerational perspectives. Trends Endocrin. Metab. 21:199-205. https://doi.org/10.1016/j.tem.2009.12.008
  14. Jia Y., R. Cong, R. Li, X. Yang, Q. Sun, N. Parvizi, and R. Zhao. 2012. Maternal low-protein diet induces gender-dependent changes in epigenetic regulation of the glucose-6-phosphatase gene in newborn piglet liver. J. Nutr. 142:1659-1665. https://doi.org/10.3945/jn.112.160341
  15. Grzesiak, M., K. Knapczyk-Stwora, M. Duda, and M. Slomczynska. 2012. Elevated level of $17{\beta}$-estradiol is associated with overexpression of FSHR, CYP19A1, and CTNNB1 genes in porcine ovarian follicles after prenatal and neonatal flutamide exposure. Theriogenology 78:2050-2060. https://doi.org/10.1016/j.theriogenology.2012.07.026
  16. Ibanez, L., N. Potau, A. Ferrer, F. Rodriguez-Hierro, M. V. Marcos, and F. de Zegher. 2002. Reduced ovulation rate in adolescent girls born small for gestational age. J. Clin. Endocrinol. Metab. 87:3391-3393. https://doi.org/10.1210/jcem.87.7.8657
  17. Iwasa, T., T. Matsuzaki, M. Murakami, R. Kinouchi, G. Gereltsetseg, S. Yamamoto, A. Kuwahara, T. Yasui, and M. Irahara. 2011. Delayed puberty in prenatally glucocorticoid administered female rats occurs independently of the hypothalamic Kiss1-Kiss1R-GnRH system. Int. J. Dev. Neurosci. 29:183-188. https://doi.org/10.1016/j.ijdevneu.2010.11.001
  18. Kertesz, M., N. Iovino, U. Unnerstall, U. Gaul, and E. Segal. 2007. The role of site accessibility in microrna target recognition. Nat. Genet. 39:1278-1284. https://doi.org/10.1038/ng2135
  19. Kezele, P. and M. K. Skinner. 2003. Regulation of ovarian primordial follicle assembly and development by estrogen and progesterone: Endocrine model of follicle assembly. Endocrinology 144:3329-3337. https://doi.org/10.1210/en.2002-0131
  20. Liu X., J. Wang, R. Li, X. Yang, Q. Sun, E. Albrecht, and R. Zhao. 2011. Maternal dietary protein affects transcriptional regulation of myostatin gene distinctively at weaning and finishing stages in skeletal muscle of Meishan pigs. Epigenetics 6:899-907. https://doi.org/10.4161/epi.6.7.16005
  21. Meikle, D. and M. Westberg. 2001. Maternal nutrition and reproduction of daughters in wild house mice (Mus musculus). Reproduction 122:437-442. https://doi.org/10.1530/rep.0.1220437
  22. Sirotkin, A. V., D. Ovcharenko, R. Grossmann, M. Laukova, and M. Mlyncek. 2009. Identification of micrornas controlling human ovarian cell steroidogenesis via a genome-scale screen. J. Cell. Physiol. 219:415-420. https://doi.org/10.1002/jcp.21689
  23. Nilsson, E. E. and M. K. Skinner. 2003. Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biol. Reprod. 69:1265-1272. https://doi.org/10.1095/biolreprod.103.018671
  24. Rae, M. T., C. E. Kyle, D. W. Miller, A. J. Hammond, A. N. Brooks, and S. M. Rhind. 2002. The effects of undernutrition, in utero, on reproductive function in adult male and female sheep. Anim. Reprod. Sci. 72:63-71. https://doi.org/10.1016/S0378-4320(02)00068-4
  25. Rucker, E. B., P. Dierisseau, K. U. Wagner, L. Garrett, A. Wynshaw-Boris, J. A. Flaws, and L. Hennighausen. 2000. Bcl-x and bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol. Endocrinol. 14:1038-1052. https://doi.org/10.1210/mend.14.7.0465
  26. Sloboda, D. M., M. Hickey, and R. Hart. 2011. Reproduction in females: The role of the early life environment. Hum. Reprod. Update. 17:210-227. https://doi.org/10.1093/humupd/dmq048
  27. Sloboda, D. M., G. J. Howie, A. Pleasants, P. D. Gluckman, and M. H. Vickers. 2009. Pre- and postnatal nutritional histories influence reproductive maturation and ovarian function in the rat. Plos One 4(8):e6744. https://doi.org/10.1371/journal.pone.0006744
  28. Sun, R., L. Lei, L. Cheng, Z. F. Jin, S. J. Zu, Z. Y. Shan, Z. D. Wang, J. X. Zhang, and Z. H. Liu. 2010. Expression of GDF-9, BMP-15 and their receptors in mammalian ovary follicles. J. Mol. Histol. 41:325-332. https://doi.org/10.1007/s10735-010-9294-2
  29. Sun, Y., Y. Lin, H. Li, J. Liu, X. Sheng and W. Zhang. 2012. 2, 5-hexanedione induces human ovarian granulosa cell apoptosis through bcl-2, bax, and caspase-3 signaling pathways. Arch. Toxicol. 86:205-215. https://doi.org/10.1007/s00204-011-0745-7
  30. Tanwar, P. S., T. O'Shea, and J. R. McFarlane, 2008. In vivo evidence of role of bone morphogenetic protein-4 in the mouse ovary. Anim. Reprod. Sci. 106:232-240. https://doi.org/10.1016/j.anireprosci.2007.04.015
  31. Tomanek, M. and E. Chronowska. 2006. Immunohistochemical localization of proliferating cell nuclear antigen (PCNA) in the pig ovary. Folia Histochem. Cytobiol. 44:269-274.
  32. Torley, K. J., J. C. da Silveira, P. Smith, R. V. Anthony, D. Veeramachaneni, Q. A. Winger, and G. J. Bouma. 2011. Expression of mirnas in ovine fetal gonads: Potential role in gonadal differentiation. Reprod. Biol. Endocrinol. 9:2. https://doi.org/10.1186/1477-7827-9-2
  33. Xu, B., J. Hua, Y. Zhang, X. Jiang, H. Zhang, T. Ma, W. Zheng, R. Sun, W. Shen, J. Sha, H. J. Cooke, and Q. Shi. 2011. Proliferating cell nuclear antigen (PCNA) regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries. Plos One. 6(1):e16046. https://doi.org/10.1371/journal.pone.0016046

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